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Medication Safety Issues
Sound-alike/look-alike issues:
MethylPREDNISolone may be confused with medroxyPROGESTERone, methotrexate, predniSONE
Depo-Medrol® may be confused with Solu-Medrol®
Medrol® may be confused with Mebaral®
Solu-Medrol® may be confused with Depo-Medrol®, salmeterol, Solu-Cortef®
International issues:
Medor® may be confused with Medral® which is a brand name for omeprazole in Mexico
Pronunciation
(meth il pred NIS oh lone)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Primarily as an anti-inflammatory or immunosuppressant agent in the treatment of a variety of diseases including those of hematologic, allergic, inflammatory, neoplastic, and autoimmune origin. Prevention and treatment of graft-versus-host disease following allogeneic bone marrow transplantation.
Use: Dental
Treatment of a variety of oral diseases of allergic, inflammatory, or autoimmune origin
Pregnancy Considerations
Adverse events have been observed with corticosteroids in animal reproduction studies. Methylprednisolone crosses the placenta. Some studies have shown an association between first trimester systemic corticosteroid use and oral clefts; adverse events in the fetus/neonate have been noted in case reports following large doses of systemic corticosteroids during pregnancy. Pregnant women exposed to methylprednisolone for antirejection therapy following a transplant may contact the National Transplantation Pregnancy Registry (NTPR) at 215-955-4820. Women exposed to methylprednisolone during pregnancy for the treatment of an autoimmune disease may contact the OTIS Autoimmune Diseases Study at 877-311-8972.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Low levels of methylprednisolone are excreted in breast milk
Contraindications
Hypersensitivity to methylprednisolone or any component of the formulation; systemic fungal infection (except intra-articular injection in localized joint conditions); administration of live virus vaccines. methylprednisolone formulations containing benzyl alcohol preservative are contraindicated in infants; I.M. administration in idiopathic thrombocytopenia purpura; intrathecal administration of methylprednisolone acetate suspension
Warnings/Precautions
Concerns related to adverse effects:
• Adrenal suppression: May cause hypercorticism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Patients receiving >20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections.
• Anaphylactoid reactions: Rare cases of anaphylactoid reactions have been observed in patients receiving corticosteroids.
• Dermal changes (methylprednisolone acetate suspension): Dermal and/or subdermal skin depression may occur at the site of injection. Avoid injection or leakage into the dermis.
• Immunosuppression: Prolonged use of corticosteroids may also increase the incidence of secondary infection, cause activation of latent infections, mask acute infection (including fungal infections), prolong or exacerbate viral or parasitic infections, or limit response to vaccines. Exposure to chickenpox or measles should be avoided; corticosteroids should not be used to treat ocular herpes simplex. Corticosteroids should not be used for cerebral malaria or viral hepatitis. Close observation is required in patients with latent tuberculosis and/or TB reactivity; restrict use in active TB (only in conjunction with antituberculosis treatment). Amebiasis should be ruled out in any patient with recent travel to tropic climates or unexplained diarrhea prior to initiation of corticosteroids.
• Myopathy: Acute myopathy has been reported with high dose corticosteroids, usually in patients with neuromuscular transmission disorders; may involve ocular and/or respiratory muscles; monitor creatine kinase; recovery may be delayed.
• Kaposi's sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi's sarcoma (case reports); discontinuation may result in clinical improvement.
• Psychiatric disturbances: Corticosteroid use may cause psychiatric disturbances, including depression, euphoria, insomnia, mood swings, and personality changes. Pre-existing psychiatric conditions may be exacerbated by corticosteroid use.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with HF; long-term use has been associated with fluid retention, hypokalemia and hypertension. Cardiomegaly and congestive heart failure have been reported following concurrent use of amphotericin B and hydrocortisone for the management of fungal infections.
• Diabetes: Use with caution in patients with diabetes mellitus; may alter glucose production/regulation leading to hyperglycemia.
• Gastrointestinal disease: Use with caution in patients with GI diseases (diverticulitis, peptic ulcer, ulcerative colitis) due to perforation risk.
• Head injury: Increased mortality was observed in patients receiving high-dose I.V. methylprednisolone; high-dose corticosteroids should not be used for the management of head injury.
• Hepatic impairment: Use with caution in patients with hepatic impairment, including cirrhosis; long-term use has been associated with fluid retention.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; exacerbation of symptoms has occurred especially during initial treatment with corticosteroids.
• Myocardial infarction (MI): Use with caution following acute MI; corticosteroids have been associated with myocardial rupture.
• Ocular disease: Use with caution in patients with cataracts and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts have occurred with prolonged use. Not recommended for the treatment of optic neuritis; may increase frequency of new episodes. Consider routine eye exams in chronic users.
• Osteoporosis: Use with caution in patients with osteoporosis; high doses and/or long-term use of corticosteroids have been associated with increased bone loss and osteoporotic fractures.
• Renal impairment: Use with caution in patients with renal impairment; fluid retention may occur.
• Seizure disorders: Use with caution in patients with a history of seizure disorder; seizures have been reported with adrenal crisis.
• Thyroid disease: Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroid patients and decreases in hypothyroid ones.
Dosage form specific issues:
• Benzyl alcohol: Some dosage forms contain benzyl alcohol which has been associated with "gasping syndrome" in neonates.
Special populations:
• Elderly: Because of the risk of adverse effects, systemic corticosteroids should be used cautiously in the elderly in the smallest possible effective dose for the shortest duration.
• Pediatrics: May affect growth velocity; growth should be routinely monitored in pediatric patients.
Other warnings/precautions:
• Discontinuation of therapy: Withdraw therapy with gradual tapering of dose.
Adverse Reactions
Frequency not defined.
Cardiovascular: Arrhythmias, bradycardia, cardiac arrest, cardiomegaly, circulatory collapse, congestive heart failure, edema, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture (post MI), syncope, tachycardia, thromboembolism, vasculitis
Central nervous system: Delirium, depression, emotional instability, euphoria, hallucinations, headache, intracranial pressure increased, insomnia, malaise, mood swings, nervousness, neuritis, personality changes, psychic disorders, pseudotumor cerebri (usually following discontinuation), seizure, vertigo
Dermatologic: Acne, allergic dermatitis, alopecia, dry scaly skin, ecchymoses, edema, erythema, hirsutism, hyper-/hypopigmentation, hypertrichosis, impaired wound healing, petechiae, rash, skin atrophy, sterile abscess, skin test reaction impaired, striae, urticaria
Endocrine & metabolic: Adrenal suppression, amenorrhea, carbohydrate intolerance increased, Cushing's syndrome, diabetes mellitus, fluid retention, glucose intolerance, growth suppression (children), hyperglycemia, hyperlipidemia, hypokalemia, hypokalemic alkalosis, menstrual irregularities, negative nitrogen balance, pituitary-adrenal axis suppression, protein catabolism, sodium and water retention
Gastrointestinal: Abdominal distention, appetite increased, bowel/bladder dysfunction (after intrathecal administration), gastrointestinal hemorrhage, gastrointestinal perforation, nausea, pancreatitis, peptic ulcer, perforation of the small and large intestine, ulcerative esophagitis, vomiting, weight gain
Hematologic: Leukocytosis (transient)
Hepatic: Hepatomegaly, transaminases increased
Local: Postinjection flare (intra-articular use), thrombophlebitis
Neuromuscular & skeletal: Arthralgia, arthropathy, aseptic necrosis (femoral and humoral heads), fractures, muscle mass loss, muscle weakness, myopathy (particularly in conjunction with neuromuscular disease or neuromuscular-blocking agents), neuropathy, osteoporosis, parasthesia, tendon rupture, vertebral compression fractures, weakness
Ocular: Cataracts, exophthalmoses, glaucoma, intraocular pressure increased
Renal: Glycosuria
Respiratory: Pulmonary edema
Miscellaneous: Abnormal fat disposition, anaphylactoid reaction, anaphylaxis, angioedema, avascular necrosis, diaphoresis, hiccups, hypersensitivity reactions, infections, secondary malignancy
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Inhibits CYP2C8 (weak), 3A4 (weak)
Drug Interactions
Acetylcholinesterase Inhibitors: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Risk C: Monitor therapy
Aminoglutethimide: May increase the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
Amphotericin B: Corticosteroids (Systemic) may enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
Antacids: May decrease the bioavailability of Corticosteroids (Oral). Risk D: Consider therapy modification
Antidiabetic Agents: Corticosteroids (Systemic) may diminish the hypoglycemic effect of Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic agent use. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
Aprepitant: May increase the serum concentration of Corticosteroids (Systemic). Risk D: Consider therapy modification
Barbiturates: May increase the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Corticosteroids (Oral). Risk C: Monitor therapy
Calcitriol: Corticosteroids (Systemic) may diminish the therapeutic effect of Calcitriol. Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May decrease the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Risk C: Monitor therapy
CycloSPORINE: Corticosteroids (Systemic) may increase the serum concentration of CycloSPORINE. CycloSPORINE may increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Estrogen Derivatives: May increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy
Fluconazole: May decrease the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
Fosaprepitant: May increase the serum concentration of Corticosteroids (Systemic). The active metabolite aprepitant is likely responsible for this effect. Risk D: Consider therapy modification
Isoniazid: Corticosteroids (Systemic) may decrease the serum concentration of Isoniazid. Risk C: Monitor therapy
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Loop Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy
Macrolide Antibiotics: May decrease the metabolism of Corticosteroids (Systemic). Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin. Risk D: Consider therapy modification
Mitotane: May decrease the serum concentration of Corticosteroids (Systemic). Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Neuromuscular-Blocking Agents (Nondepolarizing): May enhance the adverse neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness, possibly progressing to polyneuropathies and myopathies, may occur. Risk D: Consider therapy modification
NSAID (COX-2 Inhibitor): Corticosteroids (Systemic) may enhance the adverse/toxic effect of NSAID (COX-2 Inhibitor). Risk C: Monitor therapy
NSAID (Nonselective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of NSAID (Nonselective). Risk C: Monitor therapy
Primidone: May increase the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
Quinolone Antibiotics: May enhance the adverse/toxic effect of Corticosteroids (Systemic). Risk of tendon-related side effects, including tendonitis and rupture, may be enhanced. Risk C: Monitor therapy
Rifamycin Derivatives: May increase the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
Salicylates: May enhance the adverse/toxic effect of Corticosteroids (Systemic). These specifically include gastrointestinal ulceration and bleeding. Corticosteroids (Systemic) may decrease the serum concentration of Salicylates. Withdrawal of corticosteroids may result in salicylate toxicity. Risk C: Monitor therapy
Thiazide Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live virus vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Warfarin: Corticosteroids (Systemic) may enhance the anticoagulant effect of Warfarin. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase gastric mucosal irritation).
Food: Methylprednisolone interferes with calcium absorption. Limit caffeine.
Herb/Nutraceutical: St John's wort may decrease methylprednisolone levels. Avoid cat's claw, echinacea (have immunostimulant properties).
Storage
Intact vials of methylprednisolone sodium succinate should be stored at controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from light. Reconstituted solutions of methylprednisolone sodium succinate should be stored at room temperature of 20°C to 25°C (68°F to 77°F) and used within 48 hours. Stability of parenteral admixture at room temperature (25°C) and at refrigeration temperature (4°C) is 48 hours.
Reconstitution
Standard diluent (Solu-Medrol®): 40 mg/50 mL D5W; 125 mg/50 mL D5W.
Minimum volume (Solu-Medrol®): 50 mL D5W.
Compatibility
Incompatible with D51/2NS; variable stability (consult detailed reference) in D5NS, D5W, LR, NS.
Y-site administration: Compatible: Acyclovir, amifostine, amiodarone, amphotericin B cholesteryl sulfate complex, aztreonam, cefepime, cisplatin, cladribine, cyclophosphamide, cytarabine, dopamine, doxorubicin, doxorubicin liposome, enalaprilat, famotidine, fludarabine, gatifloxacin, granisetron, heparin, inamrinone, linezolid, melphalan, meperidine, methotrexate, metronidazole, midazolam, morphine, piperacillin/tazobactam, remifentanil, sodium bicarbonate, tacrolimus, teniposide, theophylline, thiotepa, topotecan. Incompatible: Allopurinol, amsacrine, ciprofloxacin, docetaxel, etoposide phosphate, filgrastim, gemcitabine, ondansetron, paclitaxel, propofol, sargramostim, vinorelbine. Variable (consult detailed reference): Cisatracurium, diltiazem, heparin with hydrocortisone sodium succinate, potassium chloride, vitamin B complex with C.
Compatibility in syringe: Compatible: Diatrizoate meglumine 52% and diatrizoate sodium 8%, diatrizoate sodium 60%, granisetron, iohexol, iopamidol, iothalamate meglumine 60%, ioxaglate meglumine 39.3% and ioxaglate sodium 19.6%, metoclopramide. Incompatible: Doxapram.
Compatibility when admixed: Compatible: Chloramphenicol, cimetidine, clindamycin, dopamine, granisetron, heparin, norepinephrine, penicillin G potassium, ranitidine, theophylline, verapamil. Incompatible: Calcium gluconate, glycopyrrolate, insulin (regular), metaraminol, nafcillin, penicillin G sodium. Variable (consult detailed reference): Aminophylline, amphotericin B, cytarabine.
Mechanism of Action
In a tissue-specific manner, corticosteroids regulate gene expression subsequent to binding specific intracellular receptors and translocation into the nucleus. Corticosteroids exert a wide array of physiologic effects including modulation of carbohydrate, protein, and lipid metabolism and maintenance of fluid and electrolyte homeostasis. Moreover cardiovascular, immunologic, musculoskeletal, endocrine, and neurologic physiology are influenced by corticosteroids. Decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability.
Pharmacodynamics/Kinetics
Onset of action: Peak effect (route dependent): Oral: 1-2 hours; I.M.: 4-8 days; Intra-articular: 1 week; methylprednisolone sodium succinate is highly soluble and has a rapid effect by I.M. and I.V. routes
Duration (route dependent): Oral: 30-36 hours; I.M.: 1-4 weeks; Intra-articular: 1-5 weeks; methylprednisolone acetate has a low solubility and has a sustained I.M. effect
Distribution: Vd: 0.7-1.5 L/kg
Half-life elimination: 3-3.5 hours; reduced in obese
Excretion: Clearance: Reduced in obese
Dosage
Dosing should be based on the lesser of ideal body weight or actual body weight
Only sodium succinate may be given I.V.; methylprednisolone sodium succinate is highly soluble and has a rapid effect by I.M. and I.V. routes. Methylprednisolone acetate has a low solubility and has a sustained I.M. effect.
Children:
Acute spinal cord injury: I.V. (sodium succinate): 30 mg/kg over 15 minutes, followed in 45 minutes by a continuous infusion of 5.4 mg/kg/hour for 23 hours
Anti-inflammatory or immunosuppressive: Oral, I.M., I.V. (sodium succinate): 0.5-1.7 mg/kg/day or 5-25 mg/m2/day in divided doses every 6-12 hours; “Pulse” therapy: 15-30 mg/kg/dose over ?30 minutes given once daily for 3 days
Asthma exacerbations, including status asthmaticus (emergency medical care or hospital doses) (NIH Asthma Guidelines, NAEPP, 2007): Children <12 years: Oral, I.V.: 1-2 mg/kg/day in 2 divided doses (maximum: 60 mg/day) until peak expiratory flow is 70% of predicted or personal best
Lupus nephritis: I.V. (sodium succinate): 30 mg/kg over ?30 minutes every other day for 6 doses
Status asthmaticus: I.V. (sodium succinate): Previous NAEPP guidelines still encountered in clinical practice: Loading dose: 2 mg/kg/dose, then 0.5-1 mg/kg/dose every 6 hours for up to 5 days; Note: See new dosing guidelines for asthma exacerbations above.
Adults: Only sodium succinate may be given I.V.; methylprednisolone sodium succinate is highly soluble and has a rapid effect by I.M. and I.V. routes. Methylprednisolone acetate has a low solubility and has a sustained I.M. effect.
Acute spinal cord injury: I.V. (sodium succinate): 30 mg/kg over 15 minutes, followed in 45 minutes by a continuous infusion of 5.4 mg/kg/hour for 23 hours
Allergic conditions: Oral: Tapered-dosage schedule:
Day 1: 24 mg on day 1 administered as 8 mg before breakfast, 4 mg after lunch, 4 mg after supper, and 8 mg at bedtime OR 24 mg as a single dose or divided into 2 or 3 doses upon initiation (regardless of time of day)
Day 2: 20 mg on day 2 administered as 4 mg before breakfast, 4 mg after lunch, 4 mg after supper, and 8 mg at bedtime
Day 3: 16 mg on day 3 administered as 4 mg before breakfast, 4 mg after lunch, 4 mg after supper, and 4 mg at bedtime
Day 4: 12 mg on day 4 administered as 4 mg before breakfast, 4 mg after lunch, and 4 mg at bedtime
Day 5: 8 mg on day 5 administered as 4 mg before breakfast and 4 mg at bedtime
Day 6: 4 mg on day 6 administered as 4 mg before breakfast
Anti-inflammatory or immunosuppressive:
Oral: 2-60 mg/day in 1-4 divided doses to start, followed by gradual reduction in dosage to the lowest possible level consistent with maintaining an adequate clinical response.
I.M. (sodium succinate): 10-80 mg/day once daily
I.M. (acetate): 10-80 mg every 1-2 weeks
I.V. (sodium succinate): 10-40 mg over a period of several minutes and repeated I.V. or I.M. at intervals depending on clinical response; when high dosages are needed, give 30 mg/kg over a period ?30 minutes and may be repeated every 4-6 hours for 48 hours.
Dermatitis, acute severe: I.M. (acetate): 80-120 mg as a single dose
Dermatitis, chronic: I.M. (acetate): 40-120 mg every 5-10 days
Status asthmaticus: I.V. (sodium succinate): Loading dose: 2 mg/kg/dose, then 0.5-1 mg/kg/dose every 6 hours for up to 5 days
Lupus nephritis: High-dose “pulse” therapy: I.V. (sodium succinate): 1 g/day for 3 days
Aplastic anemia: I.V. (sodium succinate): 1 mg/kg/day or 40 mg/day (whichever dose is higher), for 4 days. After 4 days, change to oral and continue until day 10 or until symptoms of serum sickness resolve, then rapidly reduce over approximately 2 weeks.
Pneumocystis pneumonia in AIDS patients: I.V.: 30 mg twice daily for 5 days, then 30 mg once daily for 5 days, then 15 mg once daily for 11 days
Intra-articular (acetate): Administer every 1-5 weeks.
Large joints: 20-80 mg
Small joints: 4-10 mg
Intralesional (acetate): 20-60 mg every 1-5 weeks
Dosage: Combination Regimens
Brain tumors: 8 in 1 (Brain Tumors)
Leukemia, acute lymphocytic: Hyper-CVAD (Leukemia, Acute Lymphocytic)
Lymphoma, non-Hodgkin's: ESHAP
Retinoblastoma: 8 in 1 (Retinoblastoma)
Dental Usual Dosing
Anti-inflammatory or immunosuppressive: Adults: Oral: 2-60 mg/day in 1-4 divided doses to start, followed by gradual reduction in dosage to the lowest possible level consistent with maintaining an adequate clinical response.
Administration: Oral
Administer with meals to decrease GI upset. Give daily dose in the morning to mimic normal peak blood levels.
Administration: I.V.
Only sodium succinate formulation may be given I.V. Acetate salt should not be given I.V.
Parenteral: Methylprednisolone sodium succinate may be administered I.M. or I.V.; I.V. administration may be IVP over one to several minutes or IVPB or continuous I.V. infusion.
I.V.: Succinate:
Low dose: ?1.8 mg/kg or ?125 mg/dose: I.V. push over 3-15 minutes
Moderate dose: ?2 mg/kg or 250 mg/dose: I.V. over 15-30 minutes
High dose: 15 mg/kg or ?500 mg/dose: I.V. over ?30 minutes
Doses >15 mg/kg or ?1 g: Administer over 1 hour
Do not administer high-dose I.V. push; hypotension, cardiac arrhythmia, and sudden death have been reported in patients given high-dose methylprednisolone I.V. push (>0.5 g over <10 minutes). Intermittent infusion over 15-60 minutes; maximum concentration: I.V. push 125 mg/mL.
I.M.: Acetate: Avoid injection into the deltoid muscle due to a high incidence of subcutaneous atrophy. Do not inject into areas that have evidence of acute local infection.
Administration: Topical
For external use only. Apply sparingly.
Administration: I.V. Detail
pH: 7-8 (adjusted with sodium hydroxide)
Monitoring Parameters
Blood pressure, blood glucose, electrolytes
Test Interactions
Interferes with skin tests
Dietary Considerations
Take with meals to decrease GI upset.; need diet rich in pyridoxine, vitamin C, vitamin D, folate, calcium, phosphorus, and protein.
Patient Education
Maintain adequate nutritional intake; consult prescriber for possibility of special dietary instructions. If you have diabetes, monitor serum glucose closely and notify prescriber of any changes; this medication can alter glycemic response. Avoid alcohol. Inform prescriber if you are experiencing unusual stress; dosage may need to be adjusted. You will be susceptible to infection (avoid crowds and and exposure to infection). You may experience insomnia or nervousness; use caution when driving or engaging in tasks requiring alertness until response to drug is known. Report increased pain, swelling, or redness in area being treated; excessive or sudden weight gain; swelling of extremities; respiratory difficulty; muscle pain or weakness; change in menstrual pattern; vision changes; signs of hyperglycemia; signs of infection (eg, fever, chills, mouth sores, perianal itching, vaginal discharge); blackened stool; other persistent side effects; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
Oral: Take as directed, with food or milk. Take once-a-day dose in the morning. Do not take more than prescribed or discontinue without consulting prescriber.
Intra-articular: Refrain from excessive use of joint following therapy, even if pain is gone.
Geriatric Considerations
Because of the risk of adverse effects, systemic corticosteroids should be used cautiously in the elderly, in the smallest possible dose, and for the shortest possible time.
Additional Information
Sodium content of 1 g sodium succinate injection: 2.01 mEq; 53 mg of sodium succinate salt is equivalent to 40 mg of methylprednisolone base
Methylprednisolone acetate: Depo-Medrol®
Methylprednisolone sodium succinate: Solu-Medrol®
Anesthesia and Critical Care Concerns/Other Considerations
Evidence-Based Information:
Neuromuscular Effects: ICU-acquired paresis was recently studied in five ICUs (three medical and two surgical ICUs) at four French hospitals. All ICU patients without pre-existing neuromuscular disease admitted from March 1999 through June 2000 were evaluated (de Jonghe, 2002). Each patient had to be mechanically-ventilated for ?7 days and was screened daily for awakening. The first day the patient was considered awake was Study Day 1. Patients with severe muscle weakness on Study Day 7 were considered to have ICU-acquired paresis. Among the 95 patients who were evaluated, about 25% developed ICU-acquired paresis. Independent predictors included female gender, the number of days with ?2 organ dysfunction, and administration of corticosteroids. Further studies may be required to verify and characterize the association between the development of ICU-acquired paresis and use of corticosteroids. Concurrent use of a corticosteroid and muscle relaxant appears to increase the risk of certain ICU myopathies; avoid or administer the corticosteroid at the lowest dose possible.
Adrenal Insufficiency: Patients will often have steroid-induced adverse effects on glucose tolerance and lipid profiles. When discontinuing steroid therapy in patients on long-term steroid supplementation, it is important that the steroid therapy be discontinued gradually. Abrupt withdrawal may result in adrenal insufficiency with hypotension and hyperkalemia. Patients on long-term steroid supplementation will require higher corticosteroid doses when subject to stress (eg, trauma, surgery, severe infection). Guidelines for glucocorticoid replacement during various surgical procedures have been published (Coursin, 2002; Salem, 1994).
Septic Shock: Annane, et al (2002) randomized 300 septic shock patients to either hydrocortisone (50 mg I.V. push every 6 hours) and fludrocortisone (50 mcg tablet daily via nasogastric tube) or matching placebos for 7 days. The mean Simplified Acute Physiology Score II (SAPS II) was 57 ± 19 in the placebo group and 60 ± 19 in the active treatment group. The Logistic Organ Dysfunction score was 9 ± 3 in the placebo group and 9 ± 3 in the active treatment group. In patients who did not appropriately respond to corticotropin (nonresponders), there were significantly fewer deaths in the active treatment group. Vasopressor therapy was withdrawn more frequently in this subset of the active treatment group. Adverse events were similar in both groups.
In the CORTICUS trial (Sprung, 2008), 484 septic shock patients were randomized within 72 hours of onset to receive either hydrocortisone (50 mg I.V. push every 6 hours) or placebo for 5 days followed by a 6-day taper. The primary endpoint was 28 day mortality in patients who did not respond to corticotropin. The SAPS II score in the treatment group was 49.5 ± 17.8 and 48.6 ± 16.7 in the placebo group. The Sequential Organ Failure Assessment scores were 10.6 ± 3.4 in the treatment group and 10.6 ± 3.2 in the placebo group. Different than the Annane study, in the patients who did not respond to corticotropin, there was no mortality difference at 28 days; 39.2% (95% CI: 30.5-47.9) mortality in the hydrocortisone group and 36.1% (95% CI: 26.9-45.3, P=0.69) mortality in the placebo group. A trend towards increased incidence of superinfection was noted in hydrocortisone patients. New septic shock episodes, hyperglycemia, and hypernatremia were more frequent in the hydrocortisone group. Hydrocortisone did not improve survival in this population of septic shock patients regardless of corticotropin response.
The 2008 Surviving Sepsis Campaign Guidelines suggest the following: Intravenous hydrocortisone be given only to adult septic shock patients after blood pressure is identified to be poorly responsive to fluid resuscitation and vasopressor therapy (Grade 2C); ACTH stimulation test not be used to identify the subset of adults with septic shock who should receive hydrocortisone (Grade 2B); patients with septic shock should not receive dexamethasone if hydrocortisone is available (Grade 2B); the addition of fludrocortisone if hydrocortisone is not available and the steroid that is substituted does not have significant mineralocorticoid activity (Grade 2C); doses of corticosteroids comparable to >300 mg hydrocortisone daily not be used in severe sepsis or septic shock for the purpose of treating septic shock (Grade 1A). They also recommend corticosteroids not be administered for the treatment of sepsis in the absence of shock. There is, however, no contraindication to continuing maintenance steroid therapy or to using stress dose steroids if the patient's endocrine or corticosteroid administration history warrants (Grade 1D).
The 2008 Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients recommend a diagnosis of critical illness related corticosteroid insufficiency can be made by a delta cortisol level (after 250 mcg cosyntropin) of <9 mcg/dL or a random cortisol <10 mcg/dL (Grade 2B). However, they recommend against the use of ACTH stimulation test to determine if septic shock or ARDS patients should receive steroid therapy (Grade 2B). They recommend to consider using hydrocortisone in septic shock patients who have responded poorly to resuscitation and vasopressors (Grade 2B) and glucocorticoid treatment should be tapered slowly and not stopped abruptly (Grade 2B). Dexamethasone is not recommended for the treatment of septic shock or ARDS (Grade 1B). Fludrocortisone therapy is considered optional (Grade 2B).
Cardiovascular Considerations
Long-term steroid therapy is associated with fluid retention and hypertension. Glucocorticoid agents have some mineralocorticoid activity with consequent hemodynamic effects. Patients will often have steroid-induced adverse effects on glucose tolerance and lipid profiles. In discontinuing steroid therapy in patients on long-term steroid supplementation, it is important that the steroid therapy be discontinued gradually. Abrupt withdrawal may result in adrenal insufficiency with hypotension and hyperkalemia.
Oral and intravenous steroid therapy in patients with heart failure should be administered cautiously with special attention given to signs and symptoms of fluid retention.
Although glucocorticoids can provide relief from pericarditis postmyocardial infarctions, these drugs may cause thinning of the developing scar and myocardial rupture.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Ulcerative esophagitis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Nervousness and insomnia are common; may rarely cause delirium, mood swings, euphoria, or hallucinations
Mental Health: Effects on Psychiatric Treatment
Barbiturates may increase the clearance of methylprednisolone
Nursing: Physical Assessment/Monitoring
Assess effectiveness and interactions of other medications patient may be taking. Monitor for effectiveness of therapy and adverse reactions according to dose, route, and length of therapy (especially with systemic administration). Assess knowledge/teach patient appropriate use, possible side effects/interventions, and adverse symptoms to report (ie, opportunistic infection, adrenal suppression). Instruct patients with diabetes to monitor serum glucose levels closely; corticosteroids can alter glycemic response. Dose may need to be increased if patient is experiencing higher than normal levels of stress. When discontinuing, taper dose and frequency slowly.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as sodium succinate: 40 mg, 125 mg, 500 mg, 1 g [strength expressed as base]
A-Methapred®: 40 mg, 125 mg [strength expressed as base]
Solu-Medrol®: 40 mg, 125 mg, 500 mg, 1 g, 2 g [contains benzyl alcohol (in diluent); strength expressed as base]
Solu-Medrol®: 500 mg, 1 g [strength expressed as base]
Injection, suspension, as acetate: 40 mg/mL (1 mL, 5 mL, 10 mL); 80 mg/mL (1 mL, 5 mL)
Depo-Medrol®: 20 mg/mL (5 mL); 40 mg/mL (5 mL, 10 mL); 80 mg/mL (5 mL) [contains benzyl alcohol, polysorbate 80]
Depo-Medrol®: 40 mg/mL (1 mL); 80 mg/mL (1 mL)
Tablet, oral: 4 mg
Medrol®: 2 mg, 4 mg, 8 mg, 16 mg, 32 mg
Tablet, oral [dose-pack]: 4 mg (21s) [scored]
Medrol® Dosepak™: 4 mg (21s) [scored]
Pricing: U.S. (www.drugstore.com)
Suspension (Depo-Medrol)
20 mg/mL (5): $28.65
Tablets (Medrol)
4 mg (25): $42.98
8 mg (30): $68.24
16 mg (30): $102.52
32 mg (25): $123.45
Tablets (Medrol (Pak))
4 mg (21): $37.79
Tablets (MethylPREDNISolone)
4 mg (30): $17.99
8 mg (25): $45.99
16 mg (50): $147.00
References
Abraham E and Evans T, “Corticosteroids and Septic Shock [editorial],” JAMA, 2002, 288(7):886-7.
Annane D, Sebille V, Charpentier C, et al, “Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock,” JAMA, 2002, 288(7):862-71.
Benson CA, Kaplan JE, Masur H, et al, “Treating Opportunistic Infections Among HIV-Exposed and Infected Adults and Adolescents: Recommendations from CDC, the National Institutes of Health and the HIV Medicine Association/IDSA,” MMWR Recomm Rep, 2004, 53(RR-15):1-112
Bracken MB, Shepard MJ, Collins WF, et al, “A Randomized, Controlled Trial of Methylprednisolone or Naloxone in the Treatment of Acute Spinal-Cord Injury. Results of the Second National Acute Spinal Cord Injury Study,” N Engl J Med, 1990, 322(20):1405-11.
Bratton SL, Chestnut RM, Ghajar J, et al, “Guidelines for the Management of Severe Traumatic Brain Injury. XV. Steroids,” J Neurotrauma, 2007, 24(Suppl 1):91-5
Cooper MS and Stewart PM, “Corticosteroid Insufficiency in Acutely Ill Patients,” N Engl J Med, 2003, 348(8):727-34.
Coursin DB and Wood KE, “Corticosteroid Supplementation for Adrenal Insufficiency,” JAMA, 2002, 287(2):236-40.
de Jonghe B, Sharshar T, Lefaucheur JP, et al, “Paresis Acquired in the Intensive Care Unit. A Prospective Multicenter Study,” JAMA, 2002, 288(22):2859-67.
Dellinger RP, Levy MM, Carlet JM, et al, “Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2008,” Intensive Care Med, 2008, 34(1):17-60. Available at http://www.survivingsepsis.org/system/files/images/2008_20International_20SSC_20Guidelines_1_.pdf
Edwards P, Arango M, Balica L, et al, “Final Results of MRC Crash, A Randomized Placebo-Controlled Trial of Intravenous Corticosteroid in Adults With Head Injury - Outcomes at 6 Months,” Lancet, 2005, 365(9475):1957-9.
Gamsu HR, Mullinger BM, Donnai P, et al, “Antenatal Administration of Betamethasone to Prevent Respiratory Distress Syndrome in Preterm Infants: Report of a UK Multicentre Trial,” Br J Obstet Gynaecol, 1989, 96(4):401-10.
Goedert JJ, Vitale F, Lauria C, et al, “Risk Factors for Classical Kaposi's Sarcoma,” J Natl Cancer Inst, 2002, 94(22):1712-8.
Hotchkiss RS and Karl IE, “The Pathophysiology and Treatment of Sepsis,” N Engl J Med, 2003, 348(2):138-50.
Liggins GC and Howie RN, “A Controlled Trial of Antepartum Glucocorticoid Treatment of Respiratory Distress Syndrome in Premature Infants,” Pediatrics, 1972, 50:515-25.
Marik PE, Pastores SM, Annane D, et al, “Recommendations for the Diagnosis and Management of Corticosteroid Insufficiency in Critically Ill Adult Patients: Consensus Statements From an International Task Force by the American College of Critical Care Medicine,” Crit Care Med, 2008, 36(6):1937-49.
McGee S and Hirschmann J, “Use of Corticosteroids in Treating Infectious Diseases,” Arch Intern Med, 2008, 168(10):1034-46.
National Asthma Education and Prevention Program (NAEPP), “Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma,” Clinical Practice Guidelines, National Institutes of Health, National Heart, Lung, and Blood Institute, NIH Publication No. 08-4051, prepublication 2007. Available at http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm
Ostensen M, “Optimisation of Antirheumatic Drug Treatment in Pregnancy,” Clin Pharmacokinet, 1994, 27(6):486-503.
Pradat P, Robert-Gnansia E, Di Tanna GL, et al, “First Trimester Exposure to Corticosteroids and Oral Clefts,” Birth Defects Res A Clin Mol Teratol, 2003, 67(12):968-70.
Roberts I, Yates D, Sandercock P, et al, “Effect of Intravenous Corticosteroids on Death Within 14 days in 10,008 Adults With Clinically Significant Head Injury (MRC CRASH trial): Randomised Placebo-Controlled Trial,” Lancet, 2004, 364(9442):1321-8.
Salem M, Tainsh RE Jr, Bromberg J, et al, “Perioperative Glucocorticoid Coverage. A Reassessment 42 Years After Emergence of a Problem,” Ann Surg, 1994, 219(4):416-25.
Sprung CL, Annane D, Keh D, et al, “Hydrocortisone Therapy for Patients With Septic Shock,” N Engl J Med, 2008, 358(2):111-24.
Steinberg KP, Hudson LD, Goodman RB, et al, “Efficacy and Safety of Corticosteroids for Persistent Acute Respiratory Distress Syndrome. National Heart, Lung and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network,” N Engl J Med, 2006, 354(16):1671-84.
Tornatore KM, Logue G, Venuto RC, et al, “Pharmacokinetics of Methylprednisolone in Elderly and Young Healthy Males,” J Am Geriatr Soc, 1994, 42(10):1118-22.
International Brand Names
Lexi-Comp.com
Last full review/revision October 2009
Content last modified October 2009
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